1. Field of the Invention
This invention relates to an apparatus and a method for precisely applying radioactive material onto a substrate, e.g. a brachytherapy device or the like. More particularly, the present invention relates to materials and processes for fabricating brachytherapy devices with precisely controlled amounts of radioactive or precursor materials in precisely controlled positions within such devices. The present invention marries two heretofore-disparate technologies, namely those of inkjet printing and of the fabrication of devices for brachytherapy.
2. Description of Related Art
Inkjet printing is used to print a precise amount of ink on a substrate in a precisely defined pattern. Inkjet printheads operate by one of two methods: the so-called, xe2x80x9ccontinuous inkjetxe2x80x9d process (xe2x80x9cCIJxe2x80x9d), and the xe2x80x9cdrop-on-demandxe2x80x9d process (xe2x80x9cDODxe2x80x9d). In DOD inkjet printing, there are two commonly used technologies by which ink droplet ejection is achieved. These technologies are thermal (or bubble-jet) inkjet printing and piezo-electric (or impulse) inkjet printing. In thermal inkjet printing, the energy for ink drop ejection is generated by resistor elements which are electrically heated. Such elements heat rapidly in response to electrical signals controlled by a microprocessor and create a vapor bubble which expels ink through one or more jets associated with the resistor elements. In piezo-electric inkjet printing, ink drops are ejected in response to the vibrations of a piezo-electric crystal. The piezo-electric crystal responds to an electrical signal controlled by a microprocessor.
The localized treatment of tumors and other medical conditions by the interstitial implantation of radioactive materials is a recognized treatment modality of long standing. Radioactive implants are used to provide radiation therapy in order to destroy tumors or reduce or prevent the growth of tumors. Radioactive implants are also used to prevent the growth of microscopic metastatic deposits in lymph nodes that drain the region where a tumor has been removed. Implants are also used to irradiate the postoperative tumor bed after the tumor is excised. Implantation of radioactive sources directly into solid tumors for the destruction of the tumors is used in a therapy referred to as brachytherapy.
For example, U.S. Pat. No. 3,351,049 to Lawrence discloses the use of low-energy X-ray-emitting interstitial implants as brachytherapy sources. Such implants, especially those containing palladium (Pd-103) or iodine (I-125) as the radioactive therapeutic isotope, have proven to be highly effective against solid malignancies. Excellent results have been obtained when such devices have been used against early-stage prostate cancer. These devices, or xe2x80x9cseeds,xe2x80x9d must be very small because they are typically placed in the diseased organ through a hollow needle. Once implanted in the organ, they are held in place by the surrounding tissue or stitched in place with an associated suture. A typical size for a permanent implant is a rod or cylinder 0.8 mm in diameter by 4.5 mm long. A temporary implant is typically inserted into the tissue to be treated through a hollow needle or a plastic sleeve and has approximately the same outside diameter as a permanent implant of about 0.8 mm.
An essential step in the fabrication of these tiny brachytherapy devices is the inclusion in each device of a small amount of a radioactive isotope. U.S. Pat. No. 4,323,055 to Kubiatowicz, U.S. Pat. No. 4,702,228 to Russell, U.S. Pat. No. 5,405,309 to Carden and U.S. Pat. No. 5,713,828 to Coniglione disclose technologies addressing the fabrication of brachytherapy devices. Technology disclosed in the aforementioned patents has been used to develop the processes presently used in the production of commercially available Pd-103 and I-125 seeds. The revenue from the sale of such seeds in the United States in 1997 is estimated to have been about sixty million dollars.
Notwithstanding the commercial success of present methods of brachytherapy device fabrication, the present technology does not provide ways of making brachytherapy devices that contain precisely controlled amounts of radioactive material so as to provide devices for specific orders or to provide treatment tailored to therapy requirements. Nor does it provide ways of making brachytherapy devices that contain precisely positioned amounts of radioactive material so at to provide devices with radiation fields of a controlled shape to meet therapy requirements. Nor does it provide ways of making individually produced brachytherapy devices so as to control wastage of radioactive material and meet the needs of individual customers. Nor does it provide ways of automating production of brachytherapy devices to reduce radiation exposure during manufacture, to reduce the fabrication time and to improve the uniformity of the finished product.
The inventions disclosed herein include a novel method for fabricating radiation-emitting elements, such as brachytherapy devices, and a brachytherapy device made by the novel method. The method and device disclosed herein provide improvements that can meet the various needs enumerated above.
The present invention provides a novel method for producing a radiation-emitting element consisting of a substrate onto which a radioactive fluid has been deposited in a predetermined pattern and quantity. The fluid is generally solidified (i.e. xe2x80x9ccuredxe2x80x9d) such as by polymerization or drying, before the radiation-emitting element is used.
An embodiment of the present invention comprises depositing a predetermined amount and pattern of a radioactive fluid onto a surface of a substrate as drops from a fluid-jet printhead. The technology associated with inkjet printing is generally applicable to the deposition of any fluid, whether or not such a fluid has the properties of an ink. Accordingly the term xe2x80x9cfluid-jetxe2x80x9d rather than xe2x80x9cinkjetxe2x80x9d is used herein, though the reader should understand that apparatus and methods used heretofore for inkjet printing may generally be adapted for use with the present invention, as more fully described below. Inkjet printheads reproducibly apply droplets of precise volumes to precise positions on substrates.
In particular embodiments of the present invention, individual drops of a radioactive material are deposited by a fluid-jet printhead in a predetermined pattern. Such a pattern may comprise a plurality of bands, dots or areas.
In a further embodiment of the present invention, a series of radiation-emitting elements are produced in succession, using feedback to fine tune the production of a subsequent deposited substrate based on a measurement from a previous one. The amount of radioactive fluid to be deposited on the present substrate is determined by measuring the amount or pattern of radioactive fluid deposited on a preceding substrate and accordingly adjusting the amount or pattern of radioactive fluid to be applied to the present substrate.
In a further embodiment of the present invention, the substrate has a surface over which a partially radiation-attenuating element is to be secured. This may be the cylindrical outer casing of a hollow seed brachytherapy device such as disclosed in the ""828 patent. To compensate for the attenuation of radiation by such an element, one measures the radiation-attenuating properties of the partially radiation-attenuating element; and then computes from that measurement the amount and position of the radioactive fluid to be deposited from the printhead onto the substrate so as to compensate for the measured radiation attenuating properties and thereby produce a desired radiation field external to the casing, or partially radiation-attenuating element. The radioactive fluid from the fluid-jet printhead is then deposited in predetermined amounts at predetermined locations on the surface of the substrate as so computed, and the partially radiation-attenuating element is secured in position. For further precision, the radiation-attenuating characteristics of the substrate itself are similarly measured and taken into account when the radioactive fluid is applied to the substrate.
A radioactive fluid suitable for use in a fluid-jet printhead is also an invention. Such a radioactive fluid comprises a radioisotope, e.g. in the form of a salt, a compound or a complex thereof. The radioisotope may be dissolved in a curable or dryable radiation-resistant solution, or it may be adsorbed onto a dispersible particulate carrier or powder that is dispersed in a curable radiation-resistant solution. xe2x80x9cCurablexe2x80x9d as used herein means that the fluid solidifies, e.g. by the evaporation of solvent or the forming of a polymer. Such a curable solution preferably includes a binder. Such a binder is a substance that cures to form an organic polymer (a resin) or an inorganic polymer, serving to retain the radioisotope on the substrate surface.
A particular embodiment of the radioactive fluid of the present invention includes a solution of tetraammoniumpalladium(II) hydroxide and acrylic resin in water. By tetraammoniumpalladium(II) hydroxide we mean (NH3)4Pd(OH)2. In another embodiment, the radioactive fluid comprises a radioactive powder consisting essentially of a support material onto which a radioisotope is adsorbed. Such a support material may, for example, be carbon black, activated charcoal, silica gel or, in the case of radioactive iodine, a finely ground silver zeolite. Such a radioisotope is preferably radioactive iodine or radioactive palladium. The binder is preferably an acrylic resin. In yet another embodiment, the radioactive fluid comprises a radioactive powder consisting essentially of a radioisotope such as Pd-103 in the form of palladium black (small crystals of metallic palladium) or Y-90 particles.
Various radioisotopes used in the production of brachytherapy devices that emit electro-magnetic radiation (xcex3-rays or X-rays), xcex2-particles or xcex1-particles are envisaged to be used in the present invention. Examples of such radioisotopes are isotopes that decay principally by electron capture followed by X-ray emission such as palladium-103 and iodine-125; isotopes that decay by the emission of xcex2-particles such as gold-198, gold-199, yttrium-90, and phosphorus-32; isotopes that decay with the emission of xcex2-particles and xcex3-rays such as iridium-192, and isotopes that decay with the emission of xcex1-particles such as americium-241.
Particles suitable for use in fluid-jets are generally uniform in size and have a maximum dimension not greater than about one-tenth the diameter of the jet aperture. Jet apertures of fluid jet printers are generally about 10 microns in diameter. Accordingly, particulate carriers of powders used in the present invention consist of particles small enough to easily pass through a jet of a fluid-jet printer and generally are less than 1 micron in any dimension.
A wide range of resins which may be used in the current invention are known in the inkjet and surface-coatings industries. These include, but are not limited to, acrylics, styrene acrylics, polyamides, polyvinylbutyrals, polyvinylpyrrolidones, polyketones, polyesters, phenolics, polyvinyl acetate copolymers, and maleic anhydride copolymers.
While the method of the present invention may be applied to any surface onto which it is desired to apply radioactive material, the substrate is preferably a brachytherapy support element and the method produces a brachytherapy device. When the present method is used to make a brachytherapy device, the brachytherapy support element can be of any shape, for example the shape of a tube, a rod, a suture, or a flat, convex, or concave sheet, or a sheet having a cup or bowl shape. Support elements can also be a solid body having the form of any regular or irregular solid, a sphere or an ellipsoid. The method of the present invention is particularly suited to applying radioactive material to the inner-tube of a brachytherapy device such as that disclosed in the ""828 patent.
The process of the present invention is used in another embodiment of the invention to deposit a predetermined amount and pattern of an activatable element or isotope, a xe2x80x9cprecursor material,xe2x80x9d onto a substrate using a fluid-jet printhead. In such an embodiment of the present invention, individual drops of a non-radioactive material containing an activatable isotope are deposited in a predetermined pattern to produce a precursor device. Such a predetermined pattern may comprise a plurality of bands, dots or areas. In such an embodiment, the precursor device is bombarded by suitable nuclear particles (e.g., neutron irradiation) to transmute, and thereby activate, the activatable isotope into the desired amount of radioactive material.
A non-radioactive fluid suitable for use in the aforesaid embodiment of the present invention comprises a salt, compound or complex of the activatable element or isotope either dissolved in a curable solution, or adsorbed onto a dispersible particulate carrier that is dispersed in a curable solution. The curable solution may include a binder.
A particular embodiment of the non-radioactive fluid of the present invention includes a solution of tetraammoniumpalladium(II) hydroxide and sodium silicate in water.
Precursors of radioisotopes commonly used in the production of brachytherapy precursor devices are also envisaged to be used in the present invention. A precursor isotope such as palladium-102, yttrium-89, gold-197 or iridium-191 as disclosed in the ""828 patent can be applied and then transmuted in situ by neutron irradiation.
Brachytherapy precursor devices of the invention, having precursor material on a substrate, which are activated by subsequent bombardment with appropriate nuclear particles, have a material for the substrate that is activated no more than to a minimal degree by the nuclear particles and is not otherwise modified by the radiation field present during activation.
Brachytherapy devices made by the method of the present invention have a brachytherapy support element with radioactive material applied thereon by the method of the present invention. Preferably they additionally have a substantially radiation-transparent sealing element sealingly joined to the support element to seal the surface of the brachytherapy support element and to prevent any release or escape of radioactive material from the device when in use.
Another invention disclosed herein is a brachytherapy device made by the present method. Such a brachytherapy device comprises a brachytherapy support element, radioactive material on the surface thereof, and a sealing layer to enclose and seal in the radioactive material. The support element can have the shape of a tube, a rod, a sheet, a suture, or a solid body having the form of any regular solid, a sphere or an ellipsoid. The radioactive material is applied to the surface of the support element by the process disclosed herein. The radioactive material is in the form of a pattern of a plurality of discretely applied drops of fluid. The plurality of discretely applied drops of fluid is disposed in a predetermined pattern, preferably comprising a plurality of bands, dots or areas.
CIJ technology may alternatively be used instead of DOD technology, to deposit radioactive material onto a substrate. However, if a CIJ printhead is used to implement the process of the present invention, jetted ink that is not deposited on the substrate would be captured for recycling. The high radiation intensity associated with the fluid and the economic value per unit volume are factors to be considered in designing the recycling process.
Another invention disclosed herein is an apparatus for carrying out the method of the present invention. Such an apparatus applies discrete drops of radioactive material onto a surface of a substrate. The apparatus comprises a fluid-jet printhead; a reservoir for a radioactive fluid having an opening communicating with the fluid-jet printhead; means for positioning a substrate relative to the printhead; means for moving the substrate relative to the printhead; a microprocessor that controls the firing action of the printhead and the means that positions the substrate relative to the printhead. Other embodiments of the apparatus of the present invention also incorporate means for xe2x80x9chousekeepingxe2x80x9d of the printhead (including control of fluid evaporation from the printhead nozzles, nozzle plate cleaning and means for capturing fluid jetted during priming, jet clearing and other printhead maintenance operations) and means for facilitating curing of the deposited fluid. Other embodiments further incorporate an observing means to monitor performance of the printhead.
The preferred apparatus of the present invention comprises a DOD printhead. Advantageous features of DOD printheads include smaller drop volume, reduced waste and the absence of a need to recycle a portion of the jetted fluid. However, both DOD and CIJ techniques are capable of delivering very precise volumes to a substrate in a predetermined pattern. In the present invention, the piezo-electric technique is preferred to the thermal technique because it allows the use of higher viscosity fluids, permitting greater flexibility in fluid formulation. Piezo-electric printheads are also more robust, reducing the possibility of failure from corrosion.
Another embodiment of the apparatus of the present invention also comprises a radiation-measuring device to assess the radioactivity that has been applied to a substrate and means to receive data from the measuring device and feed it to the microprocessor to provide feedback, thereby controlling the amount of radioactive material deposited by the printhead on successive brachytherapy supports.
A further embodiment of the apparatus of the present invention comprises a coating means to apply a substantially radiation-transparent sealing coat over the substrate so as to sealingly enclose the radioactive material.
The present invention has a number of features that provide advantages over previously described methods of making brachytherapy seeds. Particularly, the method disclosed herein allows precise amounts of radioactive material to be applied at an accurately determined position on a surface. When the presently described technique is used to make a brachytherapy device, a resulting device emits an accurately known amount of radiation. The radiation field is determined by the position of the radioactive material present on the device. The shape of the field can therefore be tailored by changing the position or amount of the radioactive material. The method disclosed herein advantageously facilitates such tailoring. Thus, the method disclosed herein advantageously allows radioactive material to be precisely positioned on a brachytherapy support structure so as to make a brachytherapy seed which emits a symmetrical radiation field. Alternatively, the method disclosed herein allows deposition of radioactive material so as to make a brachytherapy seed which emits a deliberately asymmetric radiation field.
A preferred embodiment of the method of the present invention permits accurate determination of the attenuation of emitted radiation by the material components of a hollow-tube brachytherapy device. In such a device, attenuation of emitted radiation, though relatively slight, is principally caused by the outer sealing tube. Additional attenuation is caused by the inner tube upon which the radiation-emitting material is deposited. Accurate determination of attenuation of radiation combined with precise control of the amount and position of radioactive material within the device allows production of brachytherapy devices that precisely meet treatment modality requirements.
In the present method, radioactive material is deposited on individual brachytherapy support structures in a one-at-a-time manner, unlike previously mentioned batch processes of the prior art. Individual production of brachytherapy devices has a therapeutic advantage, in that the actual radioactivity of each device so produced is known. Devices may be readily made by the methods disclosed herein that have particular activities suited for particular purposes. Additionally, devices may be made to fill specific orders, thus avoiding the possibility that the limited quantity of isotope available will be used to produce devices which are not purchased. For example, a physician may specify that a device of a particular activity is to be implanted on a particular day in the near future. Such a device may be produced in accordance with the present invention, with exactly the amount of radioactive material that, after decay to the specified day and time, has the desired value. Accordingly, the method disclosed herein allows precise amounts of radioactive material to be deposited on brachytherapy support structures in a one-at-a-time manner, thus making it possible for the first time to produce devices according to a prescription for a particular patient or application. Additionally, the method disclosed herein allows radioactive material to be precisely positioned on a brachytherapy support structure so as to make a brachytherapy seed which emits a consistent symmetrical or asymmetrical radiation field as required for a particular application.
A further advantage conferred by the present invention allows brachytherapy devices to be manufactured as needed, in accordance with just-in-time manufacturing principles, rather than being batch-produced so as to maintain an inventory against which orders are subsequently placed. The present invention minimizes prior-to-use decay, which is a problem for manufacturers and therapists with present methods of manufacturing brachytherapy devices because of the short radioactive half-life of the most suitable therapeutic isotopes. The present invention thus makes it possible to avoid having an inventory of unused seeds that must be securely stored and that, by radioactive decay, become therapeutically ineffective before they can be used.
These and other objects, advantages and features of the present invention will be apparent from the appended drawings and detailed description.